Figure 1. Magnified 20,000X, this colorized scanning electron micrograph (SEM) depicts a grouping of methicillin resistant Staphylococcus aureus (MRSA) bacteria (seen as tiny grape-like structures). Photo credit: CDC
Motivation and Background:
MRSA, which stands for methicillin-resistant Staphylococcus aureus, is a major pathogen and is the cause for many infections that can occur in the body, most notably on the skin. MRSA is especially difficult to treat than most staph infections because it has developed a resistance to many of the antibiotics that are regularly used to treat them. Before the 1950’s, staph infections were treated with benzylpenicillin, however there was a concern with many strains that started to develop a resistance over time . These resistant strains created an enzyme, B-lactamase, that inactivated the B-lactam antibiotic that is in benzylpenicillin. So a main goal was now to synthesize an antibiotic that was resistant to this inactivating enzyme. This was done by developing methicillin, which sterically hindered the staph B-lactamases. When methicillin began to be used clinically, methicillin-resistant S. aureus quickly arose with the first reported case being in Britain in 1961. The resistant bacteria were able to change their genomes with mutations that coded for antibiotic resistance. With the different types of antibiotics that have been used throughout the years we now face the challenge of treating multi-resistant MRSA. Anyone can get MRSA from coming into contact with an infected wound or using any item that has come in contact with an infected wound. Studies show that 1 in 3 people carry staph in their nose, however, that does not always mean that it causes an infection . Similarly, 2 in 100 people carry MRSA. Risk of infection increases in places that are over-crowded and where people share a lot of the same equipment. Particularly, the population that is most susceptible includes athletes, students in school, military personnel in barracks, and healthcare workers and patients, specifically patients that just had invasive medical and therefore weaker immune systems.
References: Bruniera, F. R.; Ferreira, F. M.; Saviolli, L. R. M. The use of vancomycin with its therapeutic and adverse effects: a review.
Many of the B-lactam antibioticswork to target penicillin-binding proteins (aka PBP’s), which are involved in the synthesis of peptidoglycan, an essential polymer for structuring bacterial cell walls. The target for vancomycin in particular is peptide subunits of peptidoglycan called D-alanyl-D-alanine. PBP’s catalyze transpeptidation reactions or cross-linking, which takes place on the external surface of the cytoplasmic membrane. Without cross-linking, the cell wall becomes too weak, which in turn causes some cytoplasmic contents to be released and so the cell dies.
Size: molecular weight of the protein 160.173 g/mol
Location: PBP’s are found in the intermembrane of the cell envelopes of many bacteria and it is usually expressed.
Function in a normal cell: PBP’s are necessary to build the cell wall and promote growth of the bacteria. Without it the cell would die and be unable to reproduce.
Drug Information:
Figure 2. Mechanism of vancomycin action and resistanceMechanism of vancomycin action and resistance: This diagram shows only one of two ways vancomycin acts against bacteria (inhibition of cell wall cross-linking) and only one of many ways that bacteria can become resistant to it. 1) Vancomycin is added to the bacterial environment while it is trying to synthesize new cell wall. Here, the cell wall strands have been synthesized, but not yet cross-linked. 2) Vancomycin recognizes and binds to the two D-ala residues on the end of the peptide chains. However, in resistant bacteria, the last D-ala residue has been replaced by a D-lactate, so vancomycin cannot bind. 3) In resistant bacteria, cross-links are successfully formed. However, in the nonresistant bacteria, the vancomycin bound to the peptide chains prevents them from interacting properly with the cell wall cross-linking enzyme. 4) In the resistant bacteria, stable cross-links are formed. In the sensitive bacteria, cross-links cannot be formed and the cell wall falls apart.
Schematic figure of drug:
Figure 3a. Chemical structure of the antibiotic vancomycin taken from PubChem.
Figure 3b. Stick figure of the vancomycin molecule. Color code: black=Carbon, white=Hydrogen, green=Chlorine, blue=Nitrogen, red=Oxygen. Model manipulated and image generated in Accelrys DS Visualizer.
Formula: C66H75Cl2N9O24
Molecular weight: 1449.265 g/mol
CAS Number: 1404-0-6
Delivery method: injection, oral Side effects: Vancomycin is sometimes used as an alternative because of the adverse side effects that it has on some patients. The most common ones being hypotension and tachycardia, phlebitis, nephrotoxicity, ototoxicity, and hypersensitive reactions. Other side effects include bladder pain, bloating, bloody or cloudy urine, convulsions, dry mouth, fever, loss of appetite, lower back or side pain, mood changes, and muscle pain or cramps.
Other names: Vancocin, Vancocin HCl, Lyphocin, Vancocin HCl Pulvulves
Maker or company: Chembase.cn, MedChemexpress (MCE), AbovChem LLC, AN PharmaTech, ChemScene, eNovation Chemicals, Chemol, Synblock Inc, Aurora Fine Chemicals LLC, ACT Chemical
Is it patented? Both Mack H. Mccormick and James M Mcguire, who both invented it vancomycin, claim the substance itself and a way of producing it.
Clinical Trials Info: There are currently 70 trials being done with the treatment of vancomycin with MRSA.
Origin:
Alternatives to this drug: trimethoprim-sulfamethoxazole, clindamycin, minocycline, or doxycycline
Miscellaneous:
Other uses: can this drug be used to treat other diseases/conditions? Vancomycin is an effective way of treating S. epidermidis, S. pneumonia, streptococcus viridans, Clostridium (intestinal infection), and Gram-negative bacilli.
Disease/Drug of interest:
methicillin-resistant Staphylococcus aureus (MRSA)/ Vancomycin (VCM)Motivation and Background:
MRSA, which stands for methicillin-resistant Staphylococcus aureus, is a major pathogen and is the cause for many infections that can occur in the body, most notably on the skin. MRSA is especially difficult to treat than most staph infections because it has developed a resistance to many of the antibiotics that are regularly used to treat them. Before the 1950’s, staph infections were treated with benzylpenicillin, however there was a concern with many strains that started to develop a resistance over time . These resistant strains created an enzyme, B-lactamase, that inactivated the B-lactam antibiotic that is in benzylpenicillin. So a main goal was now to synthesize an antibiotic that was resistant to this inactivating enzyme. This was done by developing methicillin, which sterically hindered the staph B-lactamases. When methicillin began to be used clinically, methicillin-resistant S. aureus quickly arose with the first reported case being in Britain in 1961. The resistant bacteria were able to change their genomes with mutations that coded for antibiotic resistance. With the different types of antibiotics that have been used throughout the years we now face the challenge of treating multi-resistant MRSA.Anyone can get MRSA from coming into contact with an infected wound or using any item that has come in contact with an infected wound. Studies show that 1 in 3 people carry staph in their nose, however, that does not always mean that it causes an infection . Similarly, 2 in 100 people carry MRSA. Risk of infection increases in places that are over-crowded and where people share a lot of the same equipment. Particularly, the population that is most susceptible includes athletes, students in school, military personnel in barracks, and healthcare workers and patients, specifically patients that just had invasive medical and therefore weaker immune systems.
References:
Bruniera, F. R.; Ferreira, F. M.; Saviolli, L. R. M. The use of vancomycin with its therapeutic and adverse effects: a review.
MRSA and the Workplace https://www.cdc.gov/niosh/topics/mrsa/.
Mccormick, M. H.; Mcguire, J. M.; Eli, L. C. Patent US3067099 - Vancomycin and method for its preparation.
Stapleton, P. D.; Taylor, P. W. Science Progress2002, 85 (1), 57–72.
VANCOMYCIN | C66H75Cl2N9O24 – PubChem.
External links:
https://www.cdc.gov/niosh/topics/mrsa/
Target Information:
Many of the B-lactam antibioticswork to target penicillin-binding proteins (aka PBP’s), which are involved in the synthesis of peptidoglycan, an essential polymer for structuring bacterial cell walls. The target for vancomycin in particular is peptide subunits of peptidoglycan called D-alanyl-D-alanine. PBP’s catalyze transpeptidation reactions or cross-linking, which takes place on the external surface of the cytoplasmic membrane. Without cross-linking, the cell wall becomes too weak, which in turn causes some cytoplasmic contents to be released and so the cell dies.Size: molecular weight of the protein
160.173 g/mol
Location:
PBP’s are found in the intermembrane of the cell envelopes of many bacteria and it is usually expressed.
Function in a normal cell:
PBP’s are necessary to build the cell wall and promote growth of the bacteria. Without it the cell would die and be unable to reproduce.
Drug Information:
Schematic figure of drug:
Formula:
C66H75Cl2N9O24
Molecular weight:
1449.265 g/mol
CAS Number:
1404-0-6
Delivery method:
injection, oral
Side effects:
Vancomycin is sometimes used as an alternative because of the adverse side effects that it has on some patients. The most common ones being hypotension and tachycardia, phlebitis, nephrotoxicity, ototoxicity, and hypersensitive reactions. Other side effects include bladder pain, bloating, bloody or cloudy urine, convulsions, dry mouth, fever, loss of appetite, lower back or side pain, mood changes, and muscle pain or cramps.
Other names:
Vancocin, Vancocin HCl, Lyphocin, Vancocin HCl Pulvulves
Maker or company:
Chembase.cn, MedChemexpress (MCE), AbovChem LLC, AN PharmaTech, ChemScene, eNovation Chemicals, Chemol, Synblock Inc, Aurora Fine Chemicals LLC, ACT Chemical
Is it patented?
Both Mack H. Mccormick and James M Mcguire, who both invented it vancomycin, claim the substance itself and a way of producing it.
Clinical Trials Info:
There are currently 70 trials being done with the treatment of vancomycin with MRSA.
Origin:
Alternatives to this drug:
trimethoprim-sulfamethoxazole, clindamycin, minocycline, or doxycycline
Miscellaneous:
Other uses: can this drug be used to treat other diseases/conditions?
Vancomycin is an effective way of treating S. epidermidis, S. pneumonia, streptococcus viridans, Clostridium (intestinal infection), and Gram-negative bacilli.